Neuro12 Pharmacology Flashcards
1
Q
Glaucoma drugs: alpha-agonists: Epinephrine
A
MOA: decreases aqueous humor synthesis clue to
vasoconstriction
Side effects: Mydriasis, stinging; do not use in closed-angle glaucoma
2
Q
Glaucoma drugs: alpha-agonists: Brimonidine
A
MOA: decreases aqueous humor synthesis
Side effects: No pupillary or vision changes
3
Q
Glaucoma drugs: Beta-blockers: Timolol, betaxolol, carteolol
A
MOA: decreases aqueous humor secretion
Side effects: No pupillary or vision changes
4
Q
Glaucoma drugs: Diuretics: Acetazolamide
A
MOA: decreases aqueous humor secretion due to decreased HC03-
Side effects: No pupillary or vision changes
(via inhibition of carbonic anhydrase)
5
Q
Glaucoma drugs: Cholinomimetics: Direct (pilocarpine, carbachol), indirect (physostigmine,
echothiophate)
A
MOA: increases outflow of aqueous humor; contract ciliary muscle and open trabecular meshwork; use pilocarpine in emergencies; very effective at opening meshwork into canal of Schlemm
Side effect: Miosis, cyclospasm
6
Q
Glaucoma drugs: Prostaglandin: Latanoprost (PGF2aplha)
A
MOA: increases outflow of aqueous humor
Side effect: Darkens color of iris (browning)
7
Q
Opioid analgesics: Morphine, fentanyl, codeine, heroin, methadone, meperidine, clextromethorphan, diphenoxylate
A
MOA: Act as agonists at opioid receptors (mu = morphine, delta = enkephalin, kappa = dynorphin) to modulate synaptic transmission-open K+ channels, close Ca2+ channels leads to decreased synaptic transmission. Inhibit release of ACh, NE, 5 -HT, glutamate, substance P.
Clinical use: Pain, cough suppression (dextromethorphan), diarrhea (loperamicle and diphenoxylate), acute pulmonary edema, maintenance programs for addicts (methadone).
Toxicity: Addiction, respiratory depression, constipation, miosis (pinpoint pupils), additive CNS depression with other drugs. Tolerance does not develop to miosis and constipation. Toxicity treated with naloxone or naltrexone (opioid receptor antagonist) .
8
Q
Butorphanol
A
MOA: Partial agonist at opioid m u receptors, agonist at kappa receptors.
Clinical use: Pain; causes less respiratory depression than full agonists.
Toxicity: Causes withdrawal if on full opioid agonist.
9
Q
Tramadol
A
MOA: Very weak opioid agonist; also inhibits serotonin and NE reuptake (works on multiple neurotransmitters-“tram it all” in).
Clinical use: Chronic pain
Toxicity: Similar to opioids. Decreases seizure threshold.
10
Q
Phenytoin
A
Use:
Partial Seizures: Simple, Complex
Generalized: 1st line for Tonic-clonic, 1st line prophylaxis for Status
MOA: Increases Na+ channel inactivation
Fosphenytoin for parenteral use
11
Q
Carbamazepine
A
Use:
Partial: 1st line for Simple, 1st line for Complex
Generalized: 1st line for Tonic-clonic
MOA: Increases Na+ channel inactivation
1st line for Trigeminal neuralgia
12
Q
Lamotrigine
A
Use:
Partial Seizures: Simple, Complex
Generalized: Tonic-clonic
MOA: Blocks voltage-gated Na+ channels
13
Q
Gabapentin
A
Use:
Partial Seizures: Simple, Complex
Generalized: Tonic-clonic
MOA: Designed as GABA analog, but primarily inhibits HVA Ca2+ channels
Also used for peripheral neuropathy, bipolar disorder
14
Q
Topiramate
A
Use:
Partial Seizures: Simple, Complex
Generalized: Tonic-clonic
MOA: Blocks Na+ channels, increases GABA action
15
Q
Phenobarbital
A
Use:
Partial Seizures: Simple, Complex
Generalized: Tonic-clonic
MOA: increases GABA-A action
1st line in children with partial or tonic-clonic seizures
16
Q
Valproic acid
A
Use:
Partial Seizures: Simple, Complex
Generalized: 1st line in Tonic-clonic, Absence
MOA: increases Na+ channel inactivation, increases GABA concentration
Also used for myoclonic seizures
17
Q
Ethosuximide
A
Use: 1st line for Absence Seizures
MOA: Blocks thalamic T-type Ca2+ channels
18
Q
Benzodiazepines (diazepam or lorazepam)
A
Use: 1st line for acute Status seizures
MOA: increases GABA-A action
Also used for seizures of eclampsia (1st line is MgSO4
19
Q
Tiagabine
A
Use:
Partial Seizures: Simple, Complex
MOA: Inhibits GABA reuptake
20
Q
Vigabatrin
A
Use:
Partial Seizures: Simple, Complex
MOA: Irreversibly inhibits GABA transaminase which leads to an increase GABA
21
Q
Levetiracetam
A
Use:
Partial Seizures: Simple, Complex
Generalized: Tonic-clonic
MOA: Unknown; may modulate GABA and glutamate
release
22
Q
Benzodiazepines toxicities
A
Sedation, tolerance, dependence.
23
Q
Carbamazepine toxicities
A
Diplopia, ataxia, blood dyscrasias
(agranulocytosis, aplastic anemia), liver
toxicity, teratogenesis, induction of cytochrome
P-450, SIADH, Stevens-Johnson syndrome.
Stevens-Johnson syndrome-prodrome of
malaise and fever followed by rapid onset of
erythematous/purpuric macules (oral, ocular,
genital) . Skin lesions progress to epidermal
necrosis and sloughing.
24
Q
Ethosuximide toxicities
A
GI distress, fatigue, headache, urticaria,
Stevens-Johnson syndrome.
EFGH - Ethosuximide, Fatigue, GI, Headache.
25
Phenobarbital toxicities
Sedation, tolerance, dependence, induction of cytochrome P-450.
26
Phenytoin toxicities
Nystagmus, diplopia, ataxia, sedation, gingival
hyperplasia, h irsutism, megaloblastic anemia,
teratogenesis (fetal hydantoin syndrome), SLElike
syndrome, induction of cytochrome P-450.
27
Valproic acid toxicities
GI distress, rare but fatal hepatotoxicity (measure LFTs), neural tube defects in fetus (spina bifida), tremor, weight gain.
Contraindicated in pregnancy.
28
Lamotrigine toxicities
Stevens-Johnson syndrome
29
Gabapentin toxicities
Sedation, ataxia.
30
Topiramate toxicities
Sedation, mental dulling, kidney stones, weight loss.
31
Phenytoin
Use: Tonic-clonic seizures. Also a class IB antiarrhythmic.
MOA: Use-dependent blockade of Na+ channels; decreases refractory period; inhibition of glutamate release from excitatory presynaptic neuron.
Toxicity: Nystagmus, ataxia, diplopia, sedation, SLE-like syndrome, induction of cytochrome P-450. Chronic
use produces gingival hyperplasia in children, peripheral neuropathy, hirsutism, megaloblastic
anemia ( -1- folate absorption) . Teratogenic (fetal hydantoin syndrome).
32
Barbiturates
Phenobarbital, pentobarbital, thiopental, secobarbital.
Use: Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental)
MOA: Facilitate GABA-A action by increasing duration of Cl- channel opening, thus decreasing neuron firing.
BarbiDU RATe (increases DURATion) .
Contraindicated in porphyria.
Toxicity: Dependence, additive CNS depression effects with alcohol, respiratory or cardiovascular depression (can lead to death), drug interactions owing to induction of liver microsomal enzymes (cytochrome P-450). Treat overdose with symptom management (assist respiration, increases BP) .
33
Benzodiazepines
Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam.
Use: Anxiety, spasticity, status epilepticus (lorazepam and diazepam), detoxification (especially alcohol withdrawal-DTs), night terrors, sleepwalking, general anesthetic (amnesia, muscle relaxation), hypnotic (insomnia).
MOA: Facilitate GABA-A action by increasing frequency of Cl channel
opening. decreases REM sleep. Most have long half-lives and active metabolites.
FREnzodiazepines (i FREquency) .
Short acting = TOM Thumb = Triazolam, Oxazepam, Midazolam. Highest addictive potential.
Benzos, barbs, and EtOH all bind GABA(A) -R, which is a ligand-gated chloride channel.
Toxicity: Dependence, additive CNS depression effects with alcohol. Less risk of respiratory depression and coma than with barbiturates. Treat overdose with flumazenil (competitive antagonist at GABA benzodiazepine receptor) .
34
Nonbenzodiazepine hypnotics
Zolpidem (Ambien), zaleplon, eszopiclone.
Use: Insomnia.
MOA: Act via the BZ1 receptor subtype and are reversed by flumazenil.
Toxicity: Ataxia, headaches, confusion. Short duration because of rapid metabolism by liver enzymes. Unlike older sedative-hypnotics, cause only modest day-after psychomotor depression and few amnestic effects. Lower dependence risk than benzodiazepines.
35
Anesthetics-general principles
CNS drugs must be lipid soluble (cross the blood-brain barrier) or be actively transported.
Drugs with decreased solubility in blood = rapid induction and recovery times.
Drugs with increased solubility in lipids = increased potency = 1/MAC
MAC = minimal alveolar concentration at which 50% of the population is anesthetized. Varies with age.
Examples: N20 has low blood and lipid solubility, and thus fast induction and low potency.
Halothane, in contrast, has increased lipid and blood solubility, and thus high potency and slow induction.
36
Effect of Anesthetics on Lungs
increases rate + depth of ventilation = increases gas tension
37
Effect of Anesthetics on Blood
increases blood solubility = increases blood/gas partition coefficient = increases solubility = increases gas required to saturate blood = slower onset of action
38
Effect of Anesthetics on Tissue (e.g., brain)
AV concentration gradient increases = increases solubility = increases gas required to saturate tissue = slower onset of
action
39
Inhaled anesthetics
Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide.
MOA: Unknown
Effects: Myocardial depression, respiratory depression, nausea/emesis, increases cerebral blood flow (decreases cerebral metabolic demand) .
Toxicity: Hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane), malignant
hyperthermia (rare), expansion of trapped gas (nitrous oxide) .
40
Intravenous anesthetics
Barbiturates, Benzodiazepines, Arylcyclohexylamines (Ketamine), Opiates, Propofol
41
Barbiturates: Thiopental
Thiopental: high potency, high lipid solubility, rapid entry into brain. Used for induction of anesthesia and short surgical procedures.
Effect terminated by rapid redistribution into tissue (i.e., skeletal muscle) and fat. decreases cerebral blood flow.
B. B. King on O PIATES PROPOses FOOLishly.
42
Benzodiazepines: Midazolam
Most common drug used for endoscopy; used adjunctively with gaseous anesthetics and narcotics. May cause severe postoperative respiratory depression, decreases BP
(treat overdose with flumazenil), and amnesia.
43
Arylcyclohexylamines
| Ketamine
PCP analogs that act as dissociative anesthetics. Block NMDA receptors. Cardiovascular stimulants. Cause disorientation, hallucination, and bad dreams. increases cerebral blood flow.
44
Opiates
Morphine, fentanyl used with other CNS depressants during general anesthesia.
45
Propofol
Used for rapid anesthesia induction and short procedures. Less postoperative nausea than thiopental. Potentiates GABA-A
Not recommended for home use by pop stars.
46
Local anesthetics
Esters-procaine, cocaine, tetracaine; amides-lldocalne, meplvacalne, buplvacalne (amldes have 2 l's in name)
MOA: Block Na+ channels by binding to specific receptors on inner portion of channel. Preferentially bind to activated Na+ channels, so most effective in rapidly firing neurons. 3° amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form.
Principle:
l. In infected (acidic) tissue, alkaline anesthetics are charged and cannot penetrate membrane
effectively. More anesthetic is needed in these cases.
2. Order of nerve blockade-small-diameter fibers > large diameter. Myelinated fibers > unmyelinated fibers. Overall, size factor predominates over myelination such that small myelinated fibers > small unmyelinated fibers > large myelinated fibers > large unmyelinated fibers. Order of loss-pain (lose first) > temperature > touch > pressure (lose last) .
3. Except for cocaine, given with vasoconstrictors (usually epinephrine) to enhance local action decreases bleeding, increases anesthesia by decreases systemic concentration.
Use: Minor surgical procedures, spinal anesthesia. If allergic to esters, give amides.
Toxicity: CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, hypotension, and arrhythmias (cocaine).
47
Neuromuscular blocking drugs
Used for muscle paralysis in surgery or mechanical ventilation. Selective for motor (vs. autonomic) nicotinic receptor.
48
Depolarizing Neuromuscular blocking drugs
Succinylcholine (complications include hypercalcemia and hyperkalemia) .
Reversal of blockade:
Phase I (prolonged depolarization) -no antidote. Block potentiated by cholinesterase inhibitors.
Phase II (repolarized but blocked) -antidote consists of cholinesterase inhibitors (e.g., neostigmine).
49
Nondepolarizing Neuromuscular blocking drugs
Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuronium. Competitive: compete with ACh for receptors.
Reversal of blockade-neostigmine, edrophonium, and other cholinesterase inhibitors.
50
Dantrolene
Use: Used in the treatment of malignant hyperthermia, which is caused by inhalation anesthetics (except N20) and succinylcholine. Also used to treat neuroleptic malignant syndrome (a toxicity of antipsychotic drugs) .
MOA: Prevents the release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle.
51
Parkinson's disease drugs
Parkinsonism is due to loss of dopaminergic neurons and excess cholinergic activity.
```
BALSA:
Bromocriptine
Amantadine
Levodopa (with carbidopa)
Selegiline (and COMT inhibitors)
Anti muscarinics
For essential or familial tremors, use a
```
52
Bromocriptine
Bromocriptine (ergot), pramipexole, ropinirole
(non-ergot) ; non-ergots are preferred
Strategy: Agonize dopamine receptors
53
Amantadine
Amantadine (may increase dopamine release); also used as an antiviral against influenza A and rubella; toxicity = ataxia
Strategy: increases dopamine
L-dopa/carbidopa (converted to dopamine in CNS)
54
Selegiline
Selegiline (selective MAO type B inhibitor); entacapone, tolcapone (COMT inhibitorsprevent L-dopa degradation, thereby increasing dopamine availability)
Strategy: Prevent dopamine breakdown
55
Benztropine
Benztropine (Antimuscarinic; improves tremor and rigidity but has little effect on bradykinesia)
Strategy: Curb excess cholinergic activity
Park your Mercedes-Benz
56
L-dopa (levodopa)/ carbidopa
Use: Parkinsonism
MOA: increases level of dopamine in brain. Unlike dopamine, L-dopa can cross blood-brain barrier and is converted by dopa decarboxylase in the CNS to dopamine.
Toxicity: Arrhythmias from peripheral conversion to dopamine. Long-term use can lead to dyskinesia following administration, akinesia between doses. Carbidopa, a peripheral decarboxylase inhibitor, is given with L-dopa to i the bioavailability of L-dopa in the brain and to limit peripheral side effects.
57
Selegiline
Use: Adjunctive agent to L-dopa in treatment of Parkinson's disease.
MOA: Selectively inhibits MAO-B, which preferentially metabolizes dopamine over NE and 5 -HT, thereby increasing the availability of dopamine
Toxicity: May enhance adverse effects of L-dopa.
58
Alzheimer's drugs
Memantine, Donepezil, galantamine, rivastigmine
59
Memantine
Use: Alzheimers
MOA: NMDA receptor antagonist; helps prevent excitotoxicity (mediated by Ca2+)
Toxicity: Dizziness, confusion, hallucinations.
60
Donepezil, galantamine, rivastigmine
Use: Alzheimers
MOA: Acetylcholinesterase inhibitors.
Toxicity: Nausea, dizziness, insomnia.
61
Huntington's drugs
Disease: increases dopamine, decreases GABA + ACh.
Reserpine + tetrabenazine -amine depleting.
Haloperidol: dopamine receptor antagonist.
62
Sumatriptan
Use: Acute migraine, cluster headache attacks.
MOA: 5-HTIB/ID agonist. Causes vasoconstriction,
inhibition of trigeminal activation and vasoactive peptide release. Half-life < 2 hours.
A SUMo wrestler TRIPs ANd falls on your head.
Toxicity: Coronary vasospasm (contraindicated in patients with CAD or Prinzmetal's angina), mild tingling.
63
Opioid analgesics: Morphine, fentanyl, codeine, heroin, methadone, meperidine, clextromethorphan, diphenoxylate
MOA: Act as agonists at opioid receptors (mu = morphine, delta = enkephalin, kappa = dynorphin) to modulate synaptic transmission-open K+ channels, close Ca2+ channels leads to decreased synaptic transmission. Inhibit release of ACh, NE, 5 -HT, glutamate, substance P.
Clinical use: Pain, cough suppression (dextromethorphan), diarrhea (loperamicle and diphenoxylate), acute pulmonary edema, maintenance programs for addicts (methadone).
Toxicity: Addiction, respiratory depression, constipation, miosis (pinpoint pupils), additive CNS depression with other drugs. Tolerance does not develop to miosis and constipation. Toxicity treated with naloxone or naltrexone (opioid receptor antagonist) .
64
Butorphanol
MOA: Partial agonist at opioid m u receptors, agonist at kappa receptors.
Clinical use: Pain; causes less respiratory depression than full agonists.
Toxicity: Causes withdrawal if on full opioid agonist.
65
Tramadol
MOA: Very weak opioid agonist; also inhibits serotonin and NE reuptake (works on multiple neurotransmitters-"tram it all" in).
Clinical use: Chronic pain
Toxicity: Similar to opioids. Decreases seizure threshold.
66
Phenytoin
Use:
Partial Seizures: Simple, Complex
Generalized: 1st line for Tonic-clonic, 1st line prophylaxis for Status
MOA: Increases Na+ channel inactivation
Fosphenytoin for parenteral use
67
Carbamazepine
Use:
Partial: 1st line for Simple, 1st line for Complex
Generalized: 1st line for Tonic-clonic
MOA: Increases Na+ channel inactivation
1st line for Trigeminal neuralgia
68
Lamotrigine
Use:
Partial Seizures: Simple, Complex
Generalized: Tonic-clonic
MOA: Blocks voltage-gated Na+ channels
69
Gabapentin
Use:
Partial Seizures: Simple, Complex
Generalized: Tonic-clonic
MOA: Designed as GABA analog, but primarily inhibits HVA Ca2+ channels
Also used for peripheral neuropathy, bipolar disorder
70
Topiramate
Use:
Partial Seizures: Simple, Complex
Generalized: Tonic-clonic
MOA: Blocks Na+ channels, increases GABA action
71
Phenobarbital
Use:
Partial Seizures: Simple, Complex
Generalized: Tonic-clonic
MOA: increases GABA-A action
1st line in children with partial or tonic-clonic seizures
72
Valproic acid
Use:
Partial Seizures: Simple, Complex
Generalized: 1st line in Tonic-clonic, Absence
MOA: increases Na+ channel inactivation, increases GABA concentration
Also used for myoclonic seizures
73
Ethosuximide
Use: 1st line for Absence Seizures
MOA: Blocks thalamic T-type Ca2+ channels
74
Benzodiazepines (diazepam or lorazepam)
Use: 1st line for acute Status seizures
MOA: increases GABA-A action
Also used for seizures of eclampsia (1st line is MgSO4
75
Tiagabine
Use:
Partial Seizures: Simple, Complex
MOA: Inhibits GABA reuptake
76
Vigabatrin
Use:
Partial Seizures: Simple, Complex
MOA: Irreversibly inhibits GABA transaminase which leads to an increase GABA
77
Levetiracetam
Use:
Partial Seizures: Simple, Complex
Generalized: Tonic-clonic
MOA: Unknown; may modulate GABA and glutamate
release
78
Benzodiazepines toxicities
Sedation, tolerance, dependence.
79
Carbamazepine toxicities
Diplopia, ataxia, blood dyscrasias
(agranulocytosis, aplastic anemia), liver
toxicity, teratogenesis, induction of cytochrome
P-450, SIADH, Stevens-Johnson syndrome.
Stevens-Johnson syndrome-prodrome of
malaise and fever followed by rapid onset of
erythematous/purpuric macules (oral, ocular,
genital) . Skin lesions progress to epidermal
necrosis and sloughing.
80
Ethosuximide toxicities
GI distress, fatigue, headache, urticaria,
Stevens-Johnson syndrome.
EFGH - Ethosuximide, Fatigue, GI, Headache.
81
Phenobarbital toxicities
Sedation, tolerance, dependence, induction of cytochrome P-450.
82
Phenytoin toxicities
Nystagmus, diplopia, ataxia, sedation, gingival
hyperplasia, h irsutism, megaloblastic anemia,
teratogenesis (fetal hydantoin syndrome), SLElike
syndrome, induction of cytochrome P-450.
83
Valproic acid toxicities
GI distress, rare but fatal hepatotoxicity (measure LFTs), neural tube defects in fetus (spina bifida), tremor, weight gain.
Contraindicated in pregnancy.
84
Lamotrigine toxicities
Stevens-Johnson syndrome
85
Gabapentin toxicities
Sedation, ataxia.
86
Topiramate toxicities
Sedation, mental dulling, kidney stones, weight loss.
87
Phenytoin
Use: Tonic-clonic seizures. Also a class IB antiarrhythmic.
MOA: Use-dependent blockade of Na+ channels; decreases refractory period; inhibition of glutamate release from excitatory presynaptic neuron.
Toxicity: Nystagmus, ataxia, diplopia, sedation, SLE-like syndrome, induction of cytochrome P-450. Chronic
use produces gingival hyperplasia in children, peripheral neuropathy, hirsutism, megaloblastic
anemia ( -1- folate absorption) . Teratogenic (fetal hydantoin syndrome).
88
Barbiturates
Phenobarbital, pentobarbital, thiopental, secobarbital.
Use: Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental)
MOA: Facilitate GABA-A action by increasing duration of Cl- channel opening, thus decreasing neuron firing.
BarbiDU RATe (increases DURATion) .
Contraindicated in porphyria.
Toxicity: Dependence, additive CNS depression effects with alcohol, respiratory or cardiovascular depression (can lead to death), drug interactions owing to induction of liver microsomal enzymes (cytochrome P-450). Treat overdose with symptom management (assist respiration, increases BP) .
89
Benzodiazepines
Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam.
Use: Anxiety, spasticity, status epilepticus (lorazepam and diazepam), detoxification (especially alcohol withdrawal-DTs), night terrors, sleepwalking, general anesthetic (amnesia, muscle relaxation), hypnotic (insomnia).
MOA: Facilitate GABA-A action by increasing frequency of Cl channel
opening. decreases REM sleep. Most have long half-lives and active metabolites.
FREnzodiazepines (i FREquency) .
Short acting = TOM Thumb = Triazolam, Oxazepam, Midazolam. Highest addictive potential.
Benzos, barbs, and EtOH all bind GABA(A) -R, which is a ligand-gated chloride channel.
Toxicity: Dependence, additive CNS depression effects with alcohol. Less risk of respiratory depression and coma than with barbiturates. Treat overdose with flumazenil (competitive antagonist at GABA benzodiazepine receptor) .
90
Nonbenzodiazepine hypnotics
Zolpidem (Ambien), zaleplon, eszopiclone.
Use: Insomnia.
MOA: Act via the BZ1 receptor subtype and are reversed by flumazenil.
Toxicity: Ataxia, headaches, confusion. Short duration because of rapid metabolism by liver enzymes. Unlike older sedative-hypnotics, cause only modest day-after psychomotor depression and few amnestic effects. Lower dependence risk than benzodiazepines.
91
Anesthetics-general principles
CNS drugs must be lipid soluble (cross the blood-brain barrier) or be actively transported.
Drugs with decreased solubility in blood = rapid induction and recovery times.
Drugs with increased solubility in lipids = increased potency = 1/MAC
MAC = minimal alveolar concentration at which 50% of the population is anesthetized. Varies with age.
Examples: N20 has low blood and lipid solubility, and thus fast induction and low potency.
Halothane, in contrast, has increased lipid and blood solubility, and thus high potency and slow induction.
92
Effect of Anesthetics on Lungs
increases rate + depth of ventilation = increases gas tension
93
Effect of Anesthetics on Blood
increases blood solubility = increases blood/gas partition coefficient = increases solubility = increases gas required to saturate blood = slower onset of action
94
Effect of Anesthetics on Tissue (e.g., brain)
AV concentration gradient increases = increases solubility = increases gas required to saturate tissue = slower onset of
action
95
Inhaled anesthetics
Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide.
MOA: Unknown
Effects: Myocardial depression, respiratory depression, nausea/emesis, increases cerebral blood flow (decreases cerebral metabolic demand) .
Toxicity: Hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane), malignant
hyperthermia (rare), expansion of trapped gas (nitrous oxide) .
96
Intravenous anesthetics
Barbiturates, Benzodiazepines, Arylcyclohexylamines (Ketamine), Opiates, Propofol
97
Barbiturates: Thiopental
Thiopental: high potency, high lipid solubility, rapid entry into brain. Used for induction of anesthesia and short surgical procedures.
Effect terminated by rapid redistribution into tissue (i.e., skeletal muscle) and fat. decreases cerebral blood flow.
B. B. King on O PIATES PROPOses FOOLishly.
98
Benzodiazepines: Midazolam
Most common drug used for endoscopy; used adjunctively with gaseous anesthetics and narcotics. May cause severe postoperative respiratory depression, decreases BP
(treat overdose with flumazenil), and amnesia.
99
Arylcyclohexylamines
| Ketamine
PCP analogs that act as dissociative anesthetics. Block NMDA receptors. Cardiovascular stimulants. Cause disorientation, hallucination, and bad dreams. increases cerebral blood flow.
100
Opiates
Morphine, fentanyl used with other CNS depressants during general anesthesia.
101
Propofol
Used for rapid anesthesia induction and short procedures. Less postoperative nausea than thiopental. Potentiates GABA-A
Not recommended for home use by pop stars.
102
Local anesthetics
Esters-procaine, cocaine, tetracaine; amides-lldocalne, meplvacalne, buplvacalne (amldes have 2 l's in name)
MOA: Block Na+ channels by binding to specific receptors on inner portion of channel. Preferentially bind to activated Na+ channels, so most effective in rapidly firing neurons. 3° amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form.
Principle:
l. In infected (acidic) tissue, alkaline anesthetics are charged and cannot penetrate membrane
effectively. More anesthetic is needed in these cases.
2. Order of nerve blockade-small-diameter fibers > large diameter. Myelinated fibers > unmyelinated fibers. Overall, size factor predominates over myelination such that small myelinated fibers > small unmyelinated fibers > large myelinated fibers > large unmyelinated fibers. Order of loss-pain (lose first) > temperature > touch > pressure (lose last) .
3. Except for cocaine, given with vasoconstrictors (usually epinephrine) to enhance local action decreases bleeding, increases anesthesia by decreases systemic concentration.
Use: Minor surgical procedures, spinal anesthesia. If allergic to esters, give amides.
Toxicity: CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, hypotension, and arrhythmias (cocaine).
103
Neuromuscular blocking drugs
Used for muscle paralysis in surgery or mechanical ventilation. Selective for motor (vs. autonomic) nicotinic receptor.
104
Depolarizing Neuromuscular blocking drugs
Succinylcholine (complications include hypercalcemia and hyperkalemia) .
Reversal of blockade:
Phase I (prolonged depolarization) -no antidote. Block potentiated by cholinesterase inhibitors.
Phase II (repolarized but blocked) -antidote consists of cholinesterase inhibitors (e.g., neostigmine).
105
Nondepolarizing Neuromuscular blocking drugs
Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuronium. Competitive: compete with ACh for receptors.
Reversal of blockade-neostigmine, edrophonium, and other cholinesterase inhibitors.
106
Dantrolene
Use: Used in the treatment of malignant hyperthermia, which is caused by inhalation anesthetics (except N20) and succinylcholine. Also used to treat neuroleptic malignant syndrome (a toxicity of antipsychotic drugs) .
MOA: Prevents the release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle.
107
Parkinson's disease drugs
Parkinsonism is due to loss of dopaminergic neurons and excess cholinergic activity.
```
BALSA:
Bromocriptine
Amantadine
Levodopa (with carbidopa)
Selegiline (and COMT inhibitors)
Anti muscarinics
For essential or familial tremors, use a
```
108
Bromocriptine
Bromocriptine (ergot), pramipexole, ropinirole
(non-ergot) ; non-ergots are preferred
Strategy: Agonize dopamine receptors
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Amantadine
Amantadine (may increase dopamine release); also used as an antiviral against influenza A and rubella; toxicity = ataxia
Strategy: increases dopamine
L-dopa/carbidopa (converted to dopamine in CNS)
110
Selegiline
Selegiline (selective MAO type B inhibitor); entacapone, tolcapone (COMT inhibitorsprevent L-dopa degradation, thereby increasing dopamine availability)
Strategy: Prevent dopamine breakdown
111
Benztropine
Benztropine (Antimuscarinic; improves tremor and rigidity but has little effect on bradykinesia)
Strategy: Curb excess cholinergic activity
Park your Mercedes-Benz
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L-dopa (levodopa)/ carbidopa
Use: Parkinsonism
MOA: increases level of dopamine in brain. Unlike dopamine, L-dopa can cross blood-brain barrier and is converted by dopa decarboxylase in the CNS to dopamine.
Toxicity: Arrhythmias from peripheral conversion to dopamine. Long-term use can lead to dyskinesia following administration, akinesia between doses. Carbidopa, a peripheral decarboxylase inhibitor, is given with L-dopa to i the bioavailability of L-dopa in the brain and to limit peripheral side effects.
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Selegiline
Use: Adjunctive agent to L-dopa in treatment of Parkinson's disease.
MOA: Selectively inhibits MAO-B, which preferentially metabolizes dopamine over NE and 5 -HT, thereby increasing the availability of dopamine
Toxicity: May enhance adverse effects of L-dopa.
114
Alzheimer's drugs
Memantine, Donepezil, galantamine, rivastigmine
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Memantine
Use: Alzheimers
MOA: NMDA receptor antagonist; helps prevent excitotoxicity (mediated by Ca2+)
Toxicity: Dizziness, confusion, hallucinations.
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Donepezil, galantamine, rivastigmine
Use: Alzheimers
MOA: Acetylcholinesterase inhibitors.
Toxicity: Nausea, dizziness, insomnia.
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Huntington's drugs
Disease: increases dopamine, decreases GABA + ACh.
Reserpine + tetrabenazine -amine depleting.
Haloperidol: dopamine receptor antagonist.
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Sumatriptan
Use: Acute migraine, cluster headache attacks.
MOA: 5-HTIB/ID agonist. Causes vasoconstriction,
inhibition of trigeminal activation and vasoactive peptide release. Half-life < 2 hours.
A SUMo wrestler TRIPs ANd falls on your head.
Toxicity: Coronary vasospasm (contraindicated in patients with CAD or Prinzmetal's angina), mild tingling.
